Multisensory Integration begins at or before the level of primary auditory cortex (A1) and builds over higher stages. In A1 the effect seems to be mainly a non-auditory modulation of the strength of driving auditory inputs, while in higher areas it may increasingly reflect a higher order integration of auditory and non-auditory information. In A1, auditory/non-auditory interactions use neuronal oscillations as instruments of auditory response amplification, while in higher stages, interactions also entail classic excitatory convergence. Throughout, the impact of inputs' salience (bottom-up), and that of top-down attentional control are believed to crucial. These elements - neuronal oscillations, modulatory-driving interactions, top-down control, and the underlying anatomic circuits - are ubiquitous and crucial to brain operation. Investigating them in the context of multisensory interactions affords a unique unambiguous control over the key inputs since they arise from different receptor surfaces. Our BROAD GOAL is to investigate multisensory interaction across levels of the auditory system as a general model for integrative operations in the brain. We combine anatomical analyses with electrophysiological methods indexing laminar profiles of synaptic activity and concomitant action potentials to differentiate driving auditory inputs and non-auditory modulatory inputs arising from various cortical and subcortical sources, and to determine how these input types interact physiologically during attentive discrimination. SPECIFIC AIM 1 is to characterize the mechanisms and evolution of multisensory representation across processing levels. SPECIFIC AIM 2 is to determine how cross modal cues that predict sound timing and location help auditory processing. SPECIFIC AIM 3 is to characterize the fine structure of driving and modulatory circuits in auditory cortex, emphasizing anatomical correlates of processes examined under Aims 1 and 2. Improved understanding of the critical instrumental functions of neuronal oscillations in processing of driving inputs, their manipulation by modulatory inputs, influences of stimulus salience and attention, and the underlying circuitry, will enhance the mechanistic understanding of normal hearing, as well as those underlying disruptions of hearing that contribute to a number of pathological conditions. PUBLIC HEALTH RELEVANCE: Improved mechanistic understanding of the instrumental functions of neuronal oscillations in the processing of driving inputs, their manipulation by modulatory inputs, the underlying circuitry, and the way that attention orchestrates these elements, will enhance our mechanistic understanding of perceptual/cognitive impairment specific to hearing disorders, and in a spectrum of disorders including ADHD, autism and schizophrenia, where defects in normal connectivity, disruptions of neuronal synchrony and attentional impairments are prominent